Investigating the effects of nutrient-induced developmental delay of Drosophila neural stem cells

Abstract

Proper function of the central nervous system relies on generating the correct number of cells at precise times during development. Neuroblasts, the neural stem cells of the fruit fly Drosophila, divide throughout development to produce the neurons and glia of the larval and adult nervous system. After their initial birth, neuroblasts proliferate until the end of embryogenesis when they run out of maternal nutrition and enter a period of quiescence. After hatched larvae begin feeding, they reactivate and resume proliferation to complete the development of the CNS. Prolonged periods of dietary nutrient withdrawal force larval neuroblasts into a quiescent state which is reversible upon reintroduction of amino acids to their diet, providing a system to study the effects of nutrient-induced quiescence on neuroblast proliferation in the lab. Using this model, we investigated the effects of prolonged dietary nutrient withdrawal on neuroblast proliferation by measuring the numbers of mitotic neuroblasts and the number of daughter cells they produce in brains reactivated from nutrient-induced quiescence. Both measures were delayed compared to neuroblasts in untreated control larvae despite having access to dietary nutrients for the same amount of time. We hypothesize that these proliferation deficits might represent a delay that can be overcome with more recovery time, and we are currently investigating this idea. Our study elucidates a relatively uninvestigated aspect of plasticity in the developing CNS and lays a foundation for further study of the effects of developmental delays on the adult brain.